1. Regulation of chlamydial development in culture and in vivo.2. Persistent chlamydial infection and pathogenesis.3. Pathogenesis of co-infections.

Current Research Projects:

My Ph.D. and post-doctoral training was in the molecular and cellular biology of murine
parvoviruses and ovine lentiviruses, respectively. However, my laboratory is now focused
on sexually transmitted diseases of humans. Because sexually transmitted diseases
cause enormous morbidity and mortality world wide, these studies have the potential
to significantly impact human health. Our overall goal is to understand how the sexually
transmitted bacterium, Chlamydia trachomatis, interacts with the host to produce disease. C. trachomatis is an obligate intracellular, Gram negative bacterium with a complex developmental
cycle (Fig. 1). Genital C. trachomatis infections are very common in the US, with greater than 2,800,000 new cases being reported each year. Chlamydial infection
is often inapparent and can persist for years, causing diseases ranging from mild
inflammation to infertility or life-threatening ectopic pregnancy. It is our hope that a better understanding of chlamydial pathogenesis will ultimately
lead to the development of more effective therapies and preventative interventions.

We currently have two main research projects ongoing in our laboratory. The first
project is entitled Development of an animal model of chlamydial persistence; NIAID
R21 AI082322-01; 06/01/09-05/31/12), we are testing the following two hypotheses:
i) amoxicillin-exposed, persistent chlamydiae can induce alterations in murine host
cell gene expression; and ii) amoxicillin-exposure can induce persistent (i.e. viable but non-infectious) chlamydial infection in vivo. In the course of these studies, we have: i) definitively demonstrated that viable
but non-infectious chlamydial forms are present in vivo under appropriate conditions; and ii) developed the first experimentally tractable
animal model of chlamydial persistence. This unique model will ultimately facilitate
exploration of how persistent infection impacts chlamydial pathogenesis, transmission
and antimicrobial therapy.

The second project (Characterization of a novel host pathway that regulates chlamydial
development) was previously supported by NIH/NIAID R21AI59563 and is now supported
by NIH/NIAID R01 AI095637. Previously published data from our laboratory demonstrate
that HSV-2 super-infection of C. trachomatis-infected, human genital epithelial cells profoundly alters chlamydial development.
In the course of exploring this co-infection model, we discovered that the host cell
surface protein nectin-1 is a host regulator of chlamydial development. We are currently
characterizing this novel host regulator by studying chlamydia replication in nectin-1
knockout cells and following the progression of genital tract disease in vaginally-infected
nectin-1 knockout mice. In a separate branch of this project, we have also recently
demonstrated that vaginal C. muridarum infection can protect mice against a subsequent lethal herpes simplex virus challenge.
We are currently dissecting the molecular mechanisms underlying this protection. Given
that C. trachomatis/HSV co-infections are common and that the consequences of such co-infections are
unstudied, our studies will reveal new and interesting facets of HSV/chlamydia co-pathogenesis
and will hasten development of in vivo models of polymicrobial sexually transmitted infections.

Teaching Philosophy:

As basic medical sciences educators, we have four tasks. First, we must decide what,
from the immense medical/research literature, to teach. Second, we have to present
course material in such a way that the majority of our students can comprehend it.
Third, we must evaluate how well the students have mastered the subject. Fourth, we
must motivate our students to learn the material. All four tasks are difficult and
must be mastered if one is to be an effective educator. Basic scientists tend to be
most comfortable with those tasks that are quantifiable. Thus, motivation, a fuzzy
subject at best, is usually left up to the students and is addressed, at most, by
giving a course grade. In my opinion, the issue of motivation is paramount. Motivated
students will ALWAYS accomplish more than those that are unmotivated, regardless of
other factors. Although we have little ability to determine why our students decided
to become physicians or scientists, we can substantially influence their motivation
once they enter our medical and graduate programs. So, once they are here, how do
we help keep them motivated? Though professional expectations and grades play a role,
I would suggest that an often overlooked requirement is respect. If a faculty member
puts effort into their teaching, most students will respect them for it. Such respect
provides the students with additional motivation; making them more likely to listen,
work hard and perform. Such respect is not given freely, it is earned by the efforts
an instructor makes on behalf their students. I honestly feel that, because it is
my job, I have a responsibility to my students and to the people of Tennessee to teach
to the best of my ability. This means that if I do not currently have all the necessary
skills, it is my responsibility to acquire them - a task that I take very seriously.

Student Research:

I have always considered direction of student research projects and service on student
advisory committees to be a critical component of my position in the College of Medicine.
One of the most important considerations in designing a student research project is
that it must provide a complete, well rounded scientific education. All of my students
engage in projects that require a wide range of knowledge and experimental approaches/techniques.
These projects encourage the student to: i) become proficient in many different experimental
approaches, ii) develop independence and tenacity, iii) develop the ability to properly
design and troubleshoot experiments, iv) learn how to "ask the right questions" and
v) stay current in the scientific literature. These abilities will allow students
to successfully compete for jobs and develop independent careers.

I am a firm believer in the adage work hard and play hard. Most of my out of work
activities are of the athletic variety and include backpacking, canoeing, kayaking,
camping, fishing and wildlife photography.